Citations

Abstract There is debate on the predictive value of multiday seizure cycles versus simple statistical baselines. Multidien seizure cyclicity is a prevalent, patient‐specific phenomenon with promise for epilepsy management. We challenge the assertion that cycle tracking is no better than a moving average, which is an inherently retrospective model that lags changes in seizure likelihood. This commentary compared a causal cyclic forecast to a prospectively applied moving average across a large seizure diary cohort ( n = 768) and two gold‐standard chronic EEG cohorts ( n = 24). For the EEG and diary cohorts, cycle tracking demonstrated significantly superior accuracy to the moving average for both hourly and daily forecasts ( p < 0.0001), using multiple performance metrics. These results confirm that event‐based cyclical models offer more accurate, simulated real‐world forecasts. Robust forecasting tools must prioritize the detection and modeling of seizure cycles to move beyond simple baseline performance and provide actionable clinical utility.

Abstract Cockayne Syndrome is an ultra-rare premature aging condition associated with UV sensitivity, neurocognitive decline, retinopathy, metronidazole-induced lethality, and sensorineural hearing loss. In 70% of affected patients, bi-allelic pathogenic variants in ERCC6 are identified. Although the role of ERCC6 in DNA damage repair has been studied, little is known about the mechanism for defective ERCC6 function in clinical findings, particularly hearing loss. To identify the mechanism of disease caused by pathogenic variants in ERCC6, we developed a zebrafish (Danio rerio) ercc6 loss of function model. We assessed survival after UV and metronidazole exposure, measured basal respiration rates, and evaluated mechanoelectrical transduction function and counts of lateral line hair cells. We found that UV exposure significantly reduces ercc6−/− larval viability. Metronidazole treatment results in complete lethality; wildtype controls show nearly complete survival. ercc6−/− embryos have significantly increased oxygen consumption, suggesting abnormal mitochondrial function. Phalloidin staining of lateral line hair cells with and without UV treatment shows no difference in hair cell counts per neuromast between treatment groups. Mechanoelectrical transduction function after UV exposure, measured by FM1–43 uptake, is reduced. Metronidazole lethality is reduced, oxygen consumption rates are restored, and mechanoelectrical transduction function is preserved by treatment with Mn(III)tetrakis(4-benzoic acid)porphyrin Chloride (MnTBAP), a superoxide dismutase mimetic. We propose that defective mitochondrial function and increased reactive oxygen species levels provide a mechanism for hair cell dysfunction in this model of Cockayne Syndrome. These results provide a foundation for further experiments to explore disease mechanisms and treatment modalities for this premature aging condition.

Abstract Background Agitation is a clinically significant symptom contributing to behavioral and psychological symptoms of dementia (BPSD) but is poorly understood across the different syndromes related to Frontotemporal Lobar Degeneration (FTLD). This study investigates sex differences in agitation across FTLD‐related syndromes and its relationship to various neuropsychiatric symptoms (NPS). Method We analyzed data from 1,654 participants (916 males, 738 females; average ages 65.8 and 65.9, respectively) from the National Alzheimer's Coordinating Center (NACC) and ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study with a FTLD‐related syndrome: behavioral variant FTD (bvFTD), Primary Progressive Aphasia (non‐fluent variant (nfvPPA), semantic variant (svPPA)), Corticobasal syndrome (CBS) and Progressive Supranuclear Palsy (PSP). Participants’ symptoms were assessed using the Neuropsychiatric Inventory (NPI). Prevalence ratios and odds ratios were computed to assess the likelihood of NPS comorbidities when agitation was present in males and females. Principal Component Analysis (PCA) was performed to identify NPS associated with agitation and how they varied by sex. Result Males were more likely to experience anxiety (bvFTD: p <0.001, CBS: p <0.01, PSP: p <0.0001), apathy (nfvPPA: p <0.01, PSP: p <0.01), depression (bvFTD: p <0.0001, PSP<0.01), disinhibition (nfvPPA: p <0.0001), PSP: p <0.001), and motor symptoms (bvFTD: p <0.01, CBS: p <0.01) when agitation was present. In contrast, females had a higher likelihood of experiencing disinhibition in svPPA ( p <0.001). These findings suggest that agitation is associated with a wider range of NPS in males than in females. Agitation and NPS are especially prominent in males with PSP. Conclusion This study reveals significant sex differences in NPS in FTLD‐related syndromes when agitation is present. Males and especially PSP, are more likely to experience a broader range of NPS in association with agitation. These findings underscore the need for further investigation into the underlying mechanisms driving these sex differences, particularly focusing on the neurobiological impact of agitation, the recognition of symptoms in the presence of greater behavioral disturbances, and potential variations from informant reports. Understanding these factors will provide valuable insights into the role of agitation in the presentation of NPS across FTLD‐related syndromes. Ultimately, addressing these gaps will enhance our ability to effectively treat and manage agitation in both male and female patients with FTLD‐related syndromes.

Abstract Background Staging disease severity in dementia research requires input from an informant. The Clinical Dementia Rating Sum of Boxes (CDR) is the most used instrument for staging in Alzheimer's Disease (AD); but has been expanded to stage patients with frontotemporal lobar degeneration (FTLD) with the CDR PLUS NACC‐FTLD. An informant effect on the CDR has been reported in AD. The aim of this study is to evaluate whether informant characteristics influence the CDR PLUS NACC‐FTLD in a large cohort of participants with frontotemporal dementia (FTD). Method We included participants with a FTLD‐related syndrome from the ALLFTD study. We included participants with a CDR PLUS NACC‐FTLD higher than 0, information on the Montreal Cognitive Assessment (MoCA) scores, and the Neuropsychiatric Inventory Questionnaire (NPI‐Q). We performed a conditional growth model using multilevel linear regression analysis. We performed an exploratory stratified analysis by patient sex. Result We included 1411 participants, totalling 2063 visits. The patient's age at the initial visit was 64.7±9.4 years and 44.0% were females. Females were 69.2% of the informants, and the relationship was 79.1% spouse or partner, 10.6% children, 4.1% were siblings and 6.2% other. The CDR PLUS NACC‐FTLD scores were affected by informant characteristics. The CDR PLUS NACC‐FTLD scores were 0.41 (CI 95%:0.08 to 0.75) higher with female informants. The frequency of visits was associated with a CDR PLUS NACC‐FTLD score 0.86 higher (CI 95%:0.17 to 0.56) when visiting at least once a week, 1.46 higher (CI 95%:0.46 to 2.47) when visiting daily, and 0.83 higher (CI 95%:0.06 to 1.60) when living with the patient compared with visiting less than once a week. As expected, CDR‐FLTD scores increased with lower MoCA and higher NPI‐Q scores. In the stratified analysis by sex, we found that female informant was associated with higher CDR PLUS NACC‐FTLD scores only when patients were male. Conclusion We found that the CDR PLUS NACC‐FTLD is influenced by informant sex and frequency of visits in patients with FTLD‐related syndromes. These results are similar to those observed in AD patients and underscore the need to recognize that informant characteristics may impact dementia severity scales.

Proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) disrupts key GI functions, including bowel motility. However, in many IBD patients, motility disorders persist even during remission, suggesting an irreversible ENS defect secondary to IBD. Here, we show that postinflammatory GI motility dysfunction arises from structural remodeling of the ENS, driven by a combination of neuronal loss and neurogenesis. During mucosal inflammation, enteric neurons upregulate CCL2 expression, facilitating the recruitment of monocytes into the myenteric plexus within the intestinal muscle. Monocyte-derived macrophages infiltrate the myenteric ganglia, contributing to excessive ENS remodeling and postinflammatory motility dysfunction. This neuroimmune axis is counterbalanced by a hypoxia-induced stress response in enteric neurons mediated by HIF1α. Enhancing the neuron-intrinsic hypoxia pathway limits ENS remodeling and preserves motility. In summary, this study presents a mechanistic model of postinflammatory GI motility dysfunction and proposes a therapeutic strategy to maintain ENS integrity and function during inflammation.

Abstract The Mayo Clinic Center for Clinical and Translational Science Rural Health Research Core emphasizes community engagement to address healthcare access and delivery. In 2023, the Midwest Rural Health Research Community Advisory Board (CAB) was established to guide research. Eleven of 13 researchers presenting to the CAB in 2023 completed a survey assessing influence of CAB feedback across seven domains. All reported >1 domain influenced by CAB feedback, most commonly on study design, pre-research activities and implementation. CAB feedback shaped many aspects of the rural health research process. CAB members valued seeing how their input contributed to the research process.

Abstract Objective Clinical neuropsychology is an evidence-based discipline that draws heavily from the field’s peer-reviewed journal articles. However, our scientific understanding of the methods and content that comprise the articles published in clinical neuropsychology journals is quite limited. Method A mixed methods approach was used to describe the aims, methods, and content of clinical neuropsychology’s major lifespan journals. Six-hundred articles were randomly sampled from the 2020–2024 volumes of six lifespan clinical neuropsychology journals. All articles were coded across 42 dimensions, including article type, population, design, methods, ability domains, and miscellaneous topics (e.g., brain health). The aims/scope sections of the journals were subjected to qualitative analyses, to identify relevant themes. Results The most common article content was observed in the areas of empirical/data-driven studies, cross-sectional and observational designs, older and neurological participants, cognitive testing of higher-order abilities, and psychometrics/methods. Results showed significant between-journal differences for some of these content areas at broadly medium effect sizes (e.g., experimental design, brain health topics). Qualitative analyses yielded five shared themes, suggesting that the lifespan clinical neuropsychology journals are interested in submissions on brain-behavior relationships, clinical applications, both clinical and healthy/typical populations, professional/guild matters, and multidisciplinary investigations. Conclusions The scientific content published within clinical neuropsychology’s six primary lifespan journals varies in some dimensions, but largely focuses on cross-sectional, observational studies of psychometrics and higher-order cognition. The implications of these findings for future research in clinical neuropsychology are contextualized for authors, reviewers, and readers.

Abstract INTRODUCTION Brief digital cognitive measures may be a valuable and scalable alternative to traditional tests for improving early detection and disease monitoring in patients with early‐onset Alzheimer's disease (EOAD). METHODS We examined the convergent, diagnostic, and neuroanatomical validity of Tablet‐based Cognitive Assessment Tool (TabCAT) tests in the multisite Longitudinal Early‐Onset Alzheimer's Disease Study. Four hundred seventy‐five participants from 16 sites (83 cognitively unimpaired participants, 146 individuals diagnosed with mild cognitive impairment [MCI], and 246 with mild dementia) underwent TabCAT testing, including two executive/attentional tasks (Match and Flanker) and two visuospatial tasks (Line Length and Line Orientation). RESULTS TabCAT tests showed good convergent validity with traditional pen‐and‐paper tests. Match was the most accurate TabCAT test in differentiating among clinical groups (controls vs. MCI vs. dementia) and predicting amyloid positron emission tomography (PET) positivity in clinically impaired participants. TabCAT tests were associated with regional tau PET patterns. DISCUSSION TabCAT digital measures have promise for frontline identification of patients with EOAD. Highlights Four hundred seventy‐five participants from 16 US sites underwent tablet‐based cognitive assessment. Digital tests assessed executive function and visuospatial abilities. Digital tests correlated with traditional pen‐and‐paper cognitive tests. Match (test of executive function) differentiated clinical groups. Digital tests were associated with amyloid positron emission tomography (PET) status and regional tau PET patterns.

Background The past two decades have witnessed tremendous growth in the appreciation and treatment of sacroiliac joint (SIJ) complex pain, including anatomical dissections that shed light on innervation, an appreciation for the contribution of extra-articular components to SIJ complex pain, the advent of radiofrequency ablation (RFA) and a host of minimally-invasive surgical techniques. Yet, there is no standardization of diagnosis and treatment paradigms. Methods In February 2023, the Boards of Directors for the American Academy of Pain Medicine (AAPM) and American Society of Regional Anesthesia & Pain Medicine (ASRA-PM) approved the development of multispecialty guidelines on SIJ complex pain. Thirty partner organizations with clinical and scientific interests in SIJ complex pain were identified, and formal letters of request-for-participation were sent to each, along with a request for nominees to serve on the committee. Twenty five organizations agreed to participate in addition to the Departments of Defense and Veterans Affairs. A steering committee developed 21 questions, which spanned criteria for diagnosis, non-interventional and interventional treatments including surgery, technical parameters on how to optimize results, and what constitutes positive outcomes. Questions were methodically assigned to specialized modules comprising 4–5 members with complementary expertise, who collaborated with the Subcommittee Lead and one of three Committee Chairs to develop preliminary drafts. Following thorough revisions, these drafts were subsequently submitted to the full committee for comprehensive review. A modified Delphi method was used in which the answers to questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was achieved. During a committee meeting before commencement, it was agreed that recommendations would be noted when there was >50% agreement among committee members, but that a formal recommendation would require ≥75% consensus. Results Twenty-one organizations formally endorsed the guidelines. The American Society of Anesthesiologists, and American Academy of Physical Medicine & Rehabilitation, and the North American Spine Society affirmed the benefit of the guidelines but did not officially endorse them. The American Academy of Neurology declined to affirm the benefit of the guidelines citing ‘lack of relevance to their membership.’ Per policies, while the Departments of Defense and Veterans Affairs did not formally review the guidelines for endorsement, their representatives approved them. In addition to being endorsed or the benefit affirmed by all voting organizations, complete consensus from committee members was obtained on all 21 questions. On two recommendations, there were dissensions from three societies who thought that selecting patients for sacral lateral branch RFA and minimally-invasive fusion should be based on ≥75% relief from two blocks instead of at least 50% relief from a single block before RFA, and greater than 50% pain relief with documented functional improvement after a single block before fusion. One additional society (Latin American Society of Regional Anesthesia) abstained on the statement that the evidence is stronger for extra-articular than intra-articular injections. The committee found that a battery of physical exam tests has reasonable sensitivity, but lower specificity, for identifying intra-articular but not extra-articular pain, with negative tests having greater predictive value than positive ones. Intra-articular injections have diagnostic validity for SIJ intra-articular, but not extra-articular, pain. There is unclear or negative evidence for imaging. The prevalence rates of intra-articular and extra-articular pathology are comparable, with both intra- and extra-articular steroid injections providing at least 4 weeks of relief in well-selected patients. However, the evidence is slightly stronger for extra-articular corticosteroid injections to provide short-term relief. The evidence base for non-interventional therapies is indirect, extrapolated mostly from low back pain studies. There is weak evidence supporting dextrose-based prolotherapy and platelet-rich plasma to provide at least 3 months of pain relief. There is strong evidence for sacral lateral branch RFA to provide relief for at least 6 months in individuals with extra-articular pathology, with face validity and indirect evidence from randomized trials supporting sacral lateral branch blocks as a prognostic tool. There is stronger evidence for larger lesions or more aggressive lesioning strategies than for less stringent techniques. There is weak evidence to support non-steroidal anti-inflammatory drugs to prevent neuritis after RFA, and in most cases anticoagulation does not require cessation in the periprocedural period. With an aggressive lesioning strategy, sensory stimulation provides minimal therapeutic benefit, with weak, extrapolated evidence that motor stimulation can provide safety benefit. The cut-off to designate diagnostic or prognostic blocks as positive is most commonly set at 50%, with higher values not shown to improve outcomes for more definitive procedures; for therapeutic treatment outcomes, the evidence supports a lower threshold of ≥30% pain relief or meaningful benefit on non-pain outcomes (eg, opioid cessation) for designation of a positive response. For carefully selected patients with intra-articular SIJ complex pain based on controlled blocks who have failed conservative therapies, there is weak or very weak evidence that minimally invasive SIJ fusion can provide benefit for at least one year. Conclusions SIJ complex pain remains an underappreciated source of chronic low back pain, affecting between 15% and 30% of patients with axial pain predominantly below L5. Answers to many questions were limited by low-quality evidence, indicating the need for better research. SIJ complex pain is a multifarious condition (ie, pain can be from different portions of both the intra- and extra-articular components of the joint) for which an interdisciplinary, multimodal treatment plan can optimize treatment outcomes.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more. PURPOSE To provide guidance on the recommended management of cancer in pregnant patients. METHODS A multidisciplinary Expert Panel convened and conducted a systematic review of the literature. RESULTS The systematic review identified 450 eligible studies. Much of the evidence consisted of observational data, case series, and case reports. RECOMMENDATIONS Management of cancer during pregnancy should be grounded in a values-based informed-consent process outlining maternal and fetal risks and anticipated benefits. Diagnostic evaluation should follow the as low as reasonably achievable (ALARA) principle, with timing of diagnostic studies individualized based on urgency of cancer detection, potential dangers of delay, and the balance of risks to both the pregnant patient and her embryo or fetus. Due to significant risk of harm to the developing embryo and/or fetus, systemic therapy should be deferred until the second trimester. Methotrexate, hormonal therapies, human epidermal growth factor receptor 2–targeted agents, vascular endothelial growth factor and poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and all cellular therapies are contraindicated during pregnancy, regardless of gestational age. For patients who wish to continue their pregnancy, delivery should be planned at or after 37 weeks, with the final chemotherapy dose scheduled 2-4 weeks before birth. Referral to psychosocial support services is essential to address emotional and practical challenges, reduce distress, and support shared decision making. Additional information is available at www.asco.org/survivorship-guidelines .